Abatacept Costimulatory Blockade in the Treatment of Alopecia Totalis/Universalis

Alopecia Areata is a common autoimmune disease, affecting 1% of the general population
resulting from autoimmune attack on the hair follicles and usually presents with patchy hair
loss. One third of these patients will experience spontaneous remissions within the first
year. However many patients will develop waxing and waning disease with some progressing to
alopecia totalis (total scalp hair loss) or alopecia universalis (loss of all body hair).
This population that suffers from a disfiguring disease represents a significant unmet
medical need. Alopecia totalis/universalis seldom, if ever, remits spontaneously or with
current treatment and is classified by the FDA as an Orphan Indication.

There is no FDA approved drug for alopecia areata. A recent Cochrane report concluded that
there was no evidence based support for any intervention in this disease. Standard of care
remains observation for mild disease and lesional/oral steroids for more advanced cases.

Abatacept is a soluble human fusion protein that selectively modulates the costimulatory
signal required for full T-cell activation. It is approved for the treatment of moderately
to severely active rheumatoid arthritis. It is also approved for the treatment of
moderately to severely active polyarticular juvenile idiopathic arthritis in children 6
years of age or older. Abatacept is a lyophilized powder administered as a 30 minute
intravenous infusion. Dosage, as in rheumatoid arthritis, is weight based and is fixed
throughout the course of treatment. Abatacept or placebo will be administered as a 30
minute intravenous infusion at baseline, weeks 2, 4, and every 4 weeks for 5 cycles (weeks
8, 12, 16, 20) for a total treatment period of 6 months. There will be a 6 month
observational period following the treatment period.

Inclusion Criteria:

- Must be between 18 and 75 years of age.

- Must have a diagnosis of alopecia totalis or alopecia universalis

- Must have >75% total scalp hair loss at baseline as measured using the SALT score.

- Duration of hair loss must be between 3 to 12 months.

- There may be no evidence of regrowth present at baseline.

- Subjects may be naïve to treatment or unresponsive to intralesional (IL) steroids or
other treatments for alopecia areata.

- Must be willing to avoid live vaccines while on the study medication, and within 3
months of its discontinuation.

Exclusion Criteria:

- Patients with a history of or active skin disease on the scalp such as psoriasis or
seborrheic dermatitis.

- Patients in whom the diagnosis of alopecia areata is in question.

- Patients with active medical conditions or malignancies (except adequately treated
basal or squamous cell carcinoma) that in the opinion of the investigator would
increase the risks associated with study participation, including patients with a
history of recurrent infections.

- Patients who monitor their blood glucose levels using glucose dehydrogenase
pyrrologuinolinequinone (GDH-PQQ) test strips. Blood glucose monitoring using other
methods that do not react with maltose, such as the glucose dehydrogenase nicotine
adenine dinucleotide (GDH-NAD), glucose oxidase, or glucose hexokinase test methods
are permitted.

- Patients taking TNF antagonists or other biological therapy such as anakinra.

- Women of childbearing potential who are unable or unwilling to use two forms of birth
control for the study duration.

- Women who are pregnant or nursing.

- Patients known to be HIV or hepatitis B or C positive.

- Hepatitis B surface antigen positive or Hepatitis B core antibody positive at
screening.

- Patients with latent Mycobacterium tuberculosis infection as indicated by a positive
Purified Protein Derivative [PPD] skin test. Subjects with a positive PPD skin test
and documented completion of treatment per standard medical practice for latent TB
are eligible. Subjects with a positive PPD skin test and not treated or no
documentation of completion of treatment are ineligible.

- History of incompletely treated Mycobacterium tuberculosis infection as indicated by:

- Subject's medical records documenting incomplete treatment for Mycobacterium
tuberculosis

- Subject's self-reported history of incomplete treatment for Mycobacterium
tuberculosis

- Patients with evidence of infection or skin cancer in the treated areas.

- Patients with history or evidence of hematopoietic abnormality.

- Patients with history of immunosuppression or history of recurrent serious
infections.

- Patients with a history or likely diagnosis of COPD

- Patients unwilling or unable to discontinue treatments known to affect hair regrowth
in alopecia areata.

- Patients who have been treated with intralesional steroids, systemic steroids,
anthralin, squaric acid, DPCP (diphenylcycloprophenone), protopic, minoxidil or other
medication which in the opinion of the investigator may affect hair regrowth within
one month of the baseline visit.